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JeongGoo Lee, J. Martin Heur; Inhibition of FGF2 and Zeb1 blocks injury-induced endothelial mesenchymal transition in the mouse corneal endothelium in vivo. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1457.
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FGF2-dependent fibrosis mediated through Zeb1 can drive endothelial-mesenchymal transition (EnMT) in human and mouse corneal endothelium ex vivo. We investigated whether FGF2 and Zeb1 can drive EnMT and retrocorneal membrane (RCM) formation in the mouse corneal endothelium following surgical injury in vivo.
Corneal endothelium in anesthetized mice was surgically injured in vivo under direct visualization. Secretion of FGF2 into the aqueous humor was analyzed by western blotting. Gene expression in the mouse corneal endothelium was analyzed by semi-quantitative RT-PCR. Knockdown of FGF2 and Zeb1 were done using siRNA. Col8a2 and β-actin were used as a corneal endothelial marker and a loading control, respectively.
Sequential expression of IL-1β and FGF2 were detected in the aqueous humor after surgical injury. FGF2 treatment induced expression of mesenchymal transition-related genes, Zeb1 Col1a1, Col1a2, Fn1, and Vim and their expression were completely abolished by FGF2 siRNA knockdown in the mouse corneal endothelium ex vivo. Surgical injury also induced FGF2 expression in the mouse corneal endothelium in vivo. Injury-dependent expression of FGF2, Zeb1, Col1a1, Col1a2, Fn1, and Vim were inhibited by siRNA knockdown of FGF2. Moreover, siRNA knockdown of FGF2 and Zeb1 blocked injury-dependent RCM formation in the mouse corneal endothelium in vivo.
These findings suggest that after surgical injury, FGF2 and Zeb1 mediate the expression of EnMT related genes Col1a1, Col1a2, Fn1, and Vim, and this them leads to RCM formation. This can be blocked by siRNA knockdown of FGF2 and Zeb1 in the mouse corneal endothelium in vivo.
This is a 2020 ARVO Annual Meeting abstract.
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